Controlling Reactivity and Selectivity in the Nondirected C–H Activation of Arenes with Palladium

Accounts of Chemical Research, Год журнала: 2023, Номер 56(18), С. 2459 - 2472

Опубликована: Авг. 24, 2023

ConspectusAromatic structures are widespread motifs throughout organic chemistry, and C-H activation has been recognized as a major tool for enabling their sustainable efficient functionalization. Through activation, arenes can be modified without the need prefunctionalization, leading to inherent atom- step-economic advantages over traditional methods. However, development of synthetically useful methods, several hurdles have overcome. The strength bonds necessitates sufficiently reactive catalysts, while presence multiple within substrate poses challenges in terms site-selectivity. Traditionally these addressed by control. By attaching different directing groups (DGs), reactivity respective arene was significantly enhanced DG guided metal close proximity specific bonds, resulting high introduction removal add additional steps synthetic sequence, scope reaction is limited class. complementary nondirected methods that applied broad range necessity carry functional group coordinates Pd (referred simple arenes) therefore highly desirable. intrinsically lower such substrates absence selectivity-determining pose significant solved only catalysts. Consequently, field especially with respect Pd-catalyzed remained comparatively underdeveloped when we initiated our research program 2017. At time, state-of-the-art required used large excess, precluding its use late-stage Since organopalladium species among most versatile intermediates, realized developing system, which effectively selectively activate limiting reagent, would powerful chemistry. This account summarizes groups' toward application catalytic systems offering this desired focuses explicitly on functionalization reactions arenes, where employed reagent. After an state before 2017 associated challenges, experimental mechanistic details about first arene-limited, palladium will discussed. enabled identification combination two ligands, N-heterocycle amino acid-derived ligand. Afterward discuss expansion dual-ligand approach further arene-limited transformations. Finally, describe methodologies originated from observations made during studies, namely, deuteration selective olefination method uses noncovalent interactions induce meta selectivity.

Язык: Английский

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Sterically controlled isodesmic late-stage C–H iodination of arenes

Chemical Science, Год журнала: 2023, Номер 14(16), С. 4357 - 4362

Опубликована: Янв. 1, 2023

Aryl iodides are key motifs in organic chemistry due to their versatility as linchpins metal-mediated cross-coupling reactions for synthesis and drug discovery. These scaffolds typically prepared indirectly from prefunctionalized starting materials or via electrophilic aromatic iodination protocols. methods limited specific regioisomers by inherent selectivities and/or the availability of required materials. Herein, we describe sterically controlled arenes through an isodesmic C-H/C-I bond metathesis approach enabled our dual ligand-based catalysts arene-limited nondirected C-H activation. The protocol gives direct access a complementary product spectrum with respect traditional methods. Its synthetic utility is demonstrated broad scope suitability late-stage modification.

Язык: Английский

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Harnessing the “Methyl Effect” in the Development of Novel meta-Directing Template for C–H Cyanation

ACS Catalysis, Год журнала: 2024, Номер 14(4), С. 2216 - 2228

Опубликована: Янв. 29, 2024

The significance of chelation-assisted C–H functionalization stands upon the superior site-selectivity, easy synthesis, and diverse product utility. In this work, we design a meta-directing scaffold by tuning side chain pyrimidine-based template to attain unconventional site-selectivity in anilines. A simple methyl substitution at enhances directing group (DG) efficacy significantly, leading an almost exclusive meta-selectivity. current DG further enables meta-selective cyanation aniline its higher homologues irrespective substrate electronic bias. synthetic impact methodology is highlighted with late-stage functionalizations two very popular local anesthetics butamben benzocaine. thorough experimental silico study unfolds importance effect attaining role silver carbonate mechanistic cycle.

Язык: Английский

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Pd(ii)-catalyzed meta-C–H bromination and chlorination of aniline and benzoic acid derivatives

Chemical Science, Год журнала: 2022, Номер 13(29), С. 8686 - 8692

Опубликована: Янв. 1, 2022

The classic electrophilic bromination leads to

Язык: Английский

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Asymmetric Remote meta-C–H Activation Controlled by a Chiral Ligand

ACS Catalysis, Год журнала: 2022, Номер 12(21), С. 13435 - 13445

Опубликована: Окт. 19, 2022

The use of a chiral ligand for stereocontrol has assisted the development number asymmetric functionalization proximal C–H bonds. Herein, we report ligand-controlled, remote meta-C–H activation arenes, leading to olefination and arylation hydrocinnamic acid derivatives through desymmetrization with Ac-L-Phe-OH as using Pd(II) catalyst. origins enantioselectivity were explained density functional theory calculations. larger distortion energy substrate part in bond transition structure S-TS1 is major controlling factor that disfavors formation S-enantiomer product.

Язык: Английский

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Palladium‐Catalyzed Enantioselective Isodesmic C−H Iodination of Phenylacetic Weinreb Amides

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(20)

Опубликована: Март 10, 2023

Isodesmic reactions represent mild alternatives to other chemical transformations that require harsh oxidizing agents or highly reactive intermediates. However, enantioselective isodesmic C-H functionalization is unknown and direct iodination of inert bond very rare. Rapid synthesis chiral aromatic iodides significant importance for synthetic chemistry. Herein, we report an unprecedented access iodinated phenylacetic Weinreb amides via desymmetrization kinetic resolution with PdII catalysis. Importantly, further the enantioenriched products are readily available at amide position, paving way related studies medicinal chemists.

Язык: Английский

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A Novel Approach to α‐Arylacetonitrile Skeletons via para‐Selective Alkylation of Protected Anilines

Chemistry - A European Journal, Год журнала: 2023, Номер 29(44)

Опубликована: Май 23, 2023

A ruthenium-catalyzed para-selective alkylation of protected anilines to construct α-arylacetonitrile skeletons has been reported. We firstly disclosed the ethyl 2-bromo-2-cyanopropanoate was an effective alkylating reagent in ruthenmuim-catalyzed remote-selective C-H functionalization. wide variety can be directly obtained with moderate good yields. Importantly, products contain both nitrile and ester groups guaranteeing its direct transformation into other useful synthetic units, indicating importance this method.

Язык: Английский

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Carboxyl group assisted isodesmicmeta-C–H iodination of phenethylamines, benzylamines, and 2-aryl anilines

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(15), С. 3760 - 3765

Опубликована: Янв. 1, 2023

Remote isodesmic meta -C–H iodination of phenethylamines, benzylamines, and 2-aryl anilines was enabled by an alkyl carboxyl group.

Язык: Английский

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Aryl Halides as Halogenation Reagents in the Bromination and Iodination of Arene-Tethered Diols

Organic Letters, Год журнала: 2022, Номер 24(36), С. 6510 - 6514

Опубликована: Сен. 2, 2022

Aromatic halides constitute a valuable class of building blocks that are commonly used in organic synthesis. In this study, we demonstrate usage aryl bromides and iodides C–Br or C–I bond formation. Methyl 2-bromobenzoate 2-nitrophenyl were developed as mild effective bromination iodination reagents for functionalization arene-tethered diols. This efficient cascaded catalysis can be applied to the total syntheses natural product Mafaicheenamine A Claulamine A.

Язык: Английский

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Palladium‐Catalyzed Enantioselective Isodesmic C−H Iodination of Phenylacetic Weinreb Amides

Angewandte Chemie, Год журнала: 2023, Номер 135(20)

Опубликована: Март 10, 2023

Abstract Isodesmic reactions represent mild alternatives to other chemical transformations that require harsh oxidizing agents or highly reactive intermediates. However, enantioselective isodesmic C−H functionalization is unknown and direct iodination of inert bond very rare. Rapid synthesis chiral aromatic iodides significant importance for synthetic chemistry. Herein, we report an unprecedented access iodinated phenylacetic Weinreb amides via desymmetrization kinetic resolution with Pd II catalysis. Importantly, further the enantioenriched products are readily available at amide position, paving way related studies medicinal chemists.

Язык: Английский

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