Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(7), P. 2759 - 2852

Published: Jan. 1, 2022

C-H functionalization has been emerging as a powerful method to establish carbon-carbon and carbon-heteroatom bonds. Many efforts have devoted transition-metal-catalyzed direct transformations of Metal carbenes generated in situ from transition-metal compounds diazo or its equivalents are usually applied the transient reactive intermediates furnish catalytic cycle for new C-C C-X bond formation. Using this strategy unactivated simple alkanes complex molecules can be further functionalized transformed multi-functionalized compounds. In area, carbene insertion bonds paid continuous attention. Diverse catalyst design strategies, synthetic methods, potential applications developed. This critical review will summarize advance dated up July 2021, by categories aliphatic C(sp3)-H, aryl (aromatic) C(sp2)-H, heteroaryl (heteroaromatic) C(sp2)-H bonds, alkenyl alkynyl C(sp)-H, well asymmetric more coverage given recent work. Due rapid development future directions topic also discussed. give authors an overview chemistry with focus on systems

Language: Английский

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Using Data Science To Guide Aryl Bromide Substrate Scope Analysis in a Ni/Photoredox-Catalyzed Cross-Coupling with Acetals as Alcohol-Derived Radical Sources

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(2), P. 1045 - 1055

Published: Jan. 5, 2022

Ni/photoredox catalysis has emerged as a powerful platform for C(sp2)–C(sp3) bond formation. While many of these methods typically employ aryl bromides the C(sp2) coupling partner, variety aliphatic radical sources have been investigated. In principle, reactions enable access to same product scaffolds, but it can be hard discern which method because nonstandardized sets are used in scope evaluation. Herein, we report Ni/photoredox-catalyzed (deutero)methylation and alkylation halides where benzaldehyde di(alkyl) acetals serve alcohol-derived sources. Reaction development, mechanistic studies, late-stage derivatization biologically relevant chloride, fenofibrate, presented. Then, describe integration data science techniques, including DFT featurization, dimensionality reduction, hierarchical clustering, delineate diverse succinct collection that is representative chemical space substrate class. By superimposing examples from published on this space, identify areas sparse coverage high versus low average yields, enabling comparisons between prior art new method. Additionally, demonstrate systematically selected quantify population-wide reactivity trends reveal possible functional group incompatibility with supervised machine learning.

Language: Английский

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The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD₃Reagents

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(46), P. 11751 - 11772

Published: June 2, 2021

Abstract In the field of medicinal chemistry, precise installation a trideuteromethyl group is gaining ever‐increasing attention. Site‐selective incorporation deuterated “magic methyl” can provide profound pharmacological benefits and be considered an important tool for drug optimization development. This review provides structured overview, according to trideuteromethylation reagent, currently established methods site‐selective carbon atoms. addition CD 3 , selective introduction 2 H CDH groups also considered. For all methods, corresponding mechanism scope are discussed whenever reported. As such, this starting point synthetic chemists further advance methodologies. At same time, aims guide chemists, offering them available C−CD formation strategies preparation new or modified drugs.

Language: Английский

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Catalytic ortho C–H methylation and trideuteromethylation of arylthianthrenium salts via the Catellani strategy

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(12), P. 3333 - 3340

Published: Jan. 1, 2024

We report a Pd/NBE cooperative catalyzed ortho C–H methylation and trideuteromethylation of arylthianthrenium salts, enabling the efficient synthesis wide variety (trideutero)methylated arenes in moderate to good yields.

Language: Английский

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Advances in Palladium-Catalyzed C(sp³)–H Functionalization: The Role of Traceless Directing Groups

ACS Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 15356 - 15373

Published: Oct. 3, 2024

Language: Английский

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Magnesium single-atom catalysts with superbasicity

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(6), P. 1737 - 1743

Published: May 8, 2023

Language: Английский

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Palladium-Catalyzed Annulations via Sequential C–H Activations of C(sp²)–H/C(sp³)–H or C(sp³)–H/C(sp³)–H Bonds

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 6535 - 6546

Published: April 15, 2024

Palladium-catalyzed C–H annulation reactions represent a compelling strategy to construct complex ring systems with high step economy. While there are many approaches annulate structures by activation of single bond, transformations that proceed multiple bonds less explored. This is especially true for examples where one the reacting located at an sp3 center. However, exciting developments in palladium-catalyzed continue expand scope these and provide innovative strategies challenging carbon–carbon bonds. From discoveries, sequential activations have emerged as powerful tool access through C(sp2)–H/C(sp3)–H or C(sp3)–H/C(sp3)–H In this Perspective, we showcase recent use order highlight synthetic potential activation-enabled annulations inspire future disconnections diverse scaffold synthesis.

Language: Английский

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Rhodium-Catalyzed C–H Annulation of Free Anilines with Vinylene Carbonate as a Bifunctional Synthon

Organic Letters, Journal Year: 2021, Volume and Issue: 23(22), P. 8910 - 8915

Published: Nov. 10, 2021

Chemical transformation with vinylene carbonate as an emerging synthetic unit has recently attracted considerable attention. This report is a novel conversion pattern carbonate, in which such vibrant reagent unprecedentedly acts difunctional coupling partner to complete the C-H annulation of free anilines. From commercially available substrates, this protocol leads rapid construction synthetically versatile 2-methylquinoline derivatives (43 examples) excellent functionality tolerance.

Language: Английский

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Intermolecular Difunctionalization of C,C-Palladacycles Obtained by Pd(0)-Catalyzed C–H Activation

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(23), P. 3507 - 3518

Published: Nov. 15, 2022

C,C-Palladacycles are an important class of organometallic compounds in which palladium is σ-bonded to two carbon atoms. They have three notable features that make them attractive organic synthesis and chemistry: (1) reactive intermediates can be accessed via Pd(0)-catalyzed C-H activation halides. Compared Pd(II)-catalyzed heteroatom-directed activation, catalyzed by Pd(0) has some distinct advantages. In this type catalytic reaction, the halo groups readily available halides act as traceless directing groups. Furthermore, strategy avoids use stoichiometric external oxidants. (2) differentiated reactivities from common open-chain Pd(II) species. particular, C,C-palladacycles high reactivity toward electrophiles including alkyl This unique utilized develop novel reactions. (3) C-Pd bonds, providing a platform for developing reactions.Although number reactions had been developed prior our work, scope was largely limited intramolecular cyclization Although Catellani intermolecular C,C-palladacycles, only one bonds functionalized. Our laboratory sought difunctionalization exploit their open new possibilities synthesis. Aiming synthetically useful reactions, we primarily focus on ring-forming Account, summarize laboratory's efforts obtained through activation. We wide array represent facile efficient methods cyclic compounds, functional materials drug molecules. A range studied, C(aryl),C(aryl)-palladacycles 2-halobiaryls, C(aryl),C(alkyl)-palladacycles ortho-iodo-tert-butylbenzenes or ortho-iodoanisole derivatives, those cascade found react with variety oxidants furnish Pd(IV) intermediates, such halides, aryl diazo N,N-di-tert-butyldiaziridinone, ultimately affording various structures, 5-10-membered rings, carbo- azacycles, spirocycles, fused rings. discovered. For example, unusually disilanes, leveraged disilylate very efficiency. These results should provide inspiration other C-Si bond-forming future. hope Account will stimulate further research into rich chemistry particular find practical applications bioactive molecules advance state art functionalization.

Language: Английский

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A Cascade C(sp³)−H Annulation Involving C(alkyl),C(alkyl)‐Palladacycle Intermediates

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(45)

Published: July 25, 2024

Abstract C−H bond functionalization involving C , ‐palladacycle intermediates provides a unique platform for developing novel reactions. However, the vast majority of studies have been limited to transformations (aryl), ‐palladacycles. In sharp contrast, catalytic reactions (alkyl), (alkyl)‐palladacycles rarely reported. Herein, we disclose an unprecedented cascade C(sp 3 )−H annulation (alkyl)‐palladacycles. this protocol, alkene‐tethered cycloalkenyl bromides undergo intramolecular Heck/C(sp activation generate (alkyl)‐palladacycles, which can be captured by α ‐bromoacrylic acids afford tricyclic fused pyridinediones. addition, strategy also applied indole‐tethered construct pentacyclic pyridinediones via suquential Heck dearomatization/C(sp activation/decarboxylative cyclization. Notably, removal in reaction build interesting skeleton containing four‐membered ring. Preliminary mechanistic experiments indicate that five‐membered serve as key intermediates. Meanwhile, density functional theory (DFT) calculations provided insights into pathway.

Language: Английский

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