Regiodivergent Alkylation of Pyridines: Alkyllithium Clusters Direct Chemical Reactivity

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Regiodivergent C-C bond-forming reactions are a powerful tool for constructing diverse molecular architectures from common precursors. While transition metal catalysis has dominated regioselective transformations, achieving similar precision with transition-metal-free methods remains an unmet challenge, particularly when using identical starting materials. In this work, we report transition-metal-free, regiodivergent direct alkylation of electronically unbiased pyridines 1,1-diborylalkanes as the sole alkylating agent. The key to controlling regioselectivity lies in choice alkyllithium activator 1,1-diborylalkanes: methyllithium directs predominantly C4 position, while sec-butyllithium promotes C2-alkylation. Mechanistic studies reveal that structural dynamics clusters dictate regioselectivity, tetrameric favoring C4-alkylation and dimeric preferring This method demonstrates broad substrate scope, enables late-stage functionalization complex molecules, allows sequential installation two distinct alkyl groups onto pyridine scaffold. Our approach provides versatile site-selective functionalization, offering new possibilities synthesizing alkylated pharmaceutical materials research.

Язык: Английский

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Transient Directing Groups in Metal−Organic Cooperative Catalysis

Chemistry - A European Journal, Год журнала: 2021, Номер 27(56), С. 13899 - 13952

Опубликована: Июль 19, 2021

The direct functionalization of C-H bonds is among the most fundamental chemical transformations in organic synthesis. However, when innate reactivity substrate cannot be utilized for a given single bond, this selective bond mostly relies on use directing groups that allow bringing catalyst close proximity to activated and these need installed before cleaved after transformation, which involves two additional undesired synthetic operations. These steps dramatically reduce overall impact attractiveness techniques since classical approaches based pre-functionalization are sometimes still more straightforward appealing. During past decade, different approach involving both situ installation removal group, can then often used catalytic manner, has emerged: transient group strategy. In addition its innovative character, strategy brought an unprecedented level usefulness enabled development remarkably efficient processes introduction functional onto aromatic aliphatic substrates. unlocked by will comprehensively overviewed review article.

Язык: Английский

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Transition‐Metal‐Catalyzed, Chelation‐Assisted C−H Alkenylation and Allylation of Organic Molecules with Unactivated Alkenes

Advanced Synthesis & Catalysis, Год журнала: 2022, Номер 364(13), С. 2113 - 2139

Опубликована: Май 6, 2022

Abstract Olefins are important building blocks and widely utilized in synthetic organic chemistry. Owing to its omnipresence unique reactivity, the functionalization of alkenes has become a powerful method for constructing complex molecules. In this context, direct chelation‐assisted C−H olefination at inert bonds represents most straightforward introducing alkenyl group into compounds highly regio‐ stereoselective manner. Despite remarkable advances reaction, successful transformations restricted activated or electronically biased olefins such as acrylates, styrenes, acrylamides, vinyl sulfones, phosphonates. Literature reports on with unactivated unbiased limited due poor intrinsic reactivity regioselectivity issues. significant challenges, past few years have witnessed tremendous growth. The present review describes recent allylation aromatics, alkenes, heteroaromatics via concerted‐metallation‐ deprotonation pathway.Transition metals palladium, rhodium, iridium cobalt used these kind transformations. scope, mechanistic investigation, limitation alkenylation reactions discussed elaborately. includes all reported base‐assisted pathway. magnified image

Язык: Английский

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S,O‐Ligand Promoted meta‐C−H Arylation of Anisole Derivatives via Palladium/Norbornene Catalysis

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(31)

Опубликована: Май 31, 2022

Reversing the conventional site-selectivity of C-H activation processes provides new retrosynthetic disconnections to otherwise unreactive bonds. Here, we report a catalytic system based on palladium/norbornene and an S,O-ligand for meta-C-H arylation aryl ethers that significantly outperforms previously reported systems. We demonstrate unique ability this employ alkoxyarene substrates bearing electron donating withdrawing substituents. Additionally, ortho-substituted are well tolerated, overcoming "ortho constraint", which is necessity have meta-substituent achieve high reaction efficiency, by enlisting novel norbornene mediators. Remarkably, first time monoarylation alkoxyarenes achieved efficiently enabling subsequent introduction second, different coupling partner rapidly furnish unsymmetrical terphenyls. Further insight into mechanism was isolation characterization some Pd-complexes-before after meta activation-prior evaluation their respective activities.

Язык: Английский

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Charge-controlled Pd catalysis enables the meta-C–H activation and olefination of arenes

Chem, Год журнала: 2023, Номер 9(4), С. 1004 - 1016

Опубликована: Янв. 24, 2023

The regioselective C-H activation of arenes remains one the most promising techniques for accessing highly important functionalized motifs. Such functionalizations can generally be achieved through directed and non-directed processes. approach requires a covalently attached directing group (DG) on substrate to induce reactivity selectivity therefore intrinsically leaves functional at point attachment within molecule, even after tailored DG has been removed. Conversely, methods typically suffer from regioselectivity issues, especially unbiased substrates. Herein, we report unique that employs weak charge-charge charge-dipole interactions enable meta-selective olefination address these challenges in Pd catalysis. charged moiety easily converted uncharged simple by hydrogenation or cross-coupling. In-depth mechanistic studies prove charge is responsible observed selectivity. We expect our generalizable thereby further transformations.

Язык: Английский

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

ACS Catalysis, Год журнала: 2024, Номер unknown, С. 15356 - 15373

Опубликована: Окт. 3, 2024

Язык: Английский

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Photo-Driven Traceless Directed Electron-Donor-Acceptor (EDA) Complex Initiated Radical Coupling/Dehydrogenation Tandem Reaction: Access to 1-Allyl/Benzyl-3,4-dihydroisoquinoline

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(4), С. 1050 - 1056

Опубликована: Янв. 1, 2024

A metal-free and mild one pot protocol for the traceless group directed electron–donor–acceptor (EDA) complex initiated radical coupling/dehydrogenation of arylazo-protected tetrahydroisoquinolines with benzyl/allyl bromide is reported.

Язык: Английский

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1,3-diene-based AIEgens: Stereoselective synthesis and applications

iScience, Год журнала: 2024, Номер 27(3), С. 109223 - 109223

Опубликована: Фев. 15, 2024

SummaryIn recent years, significant advancements have been made in the synthesis and application of 1,3-dienes. This specific structural motif has garnered attention from researchers materials science biology due to its unique aggregation-induced emission (AIE) properties extensive conjugation systems. The luminescent characteristics these compounds are notably influenced by geometry two double bonds. Therefore, it is essential consolidate stereoselective synthetic strategies for comprehensive review seeks elucidate diverse techniques employed attain stereo-control 1,3-diene-based AIE luminogens (AIEgens). Particular emphasis placed on comprehending determinants stereoselectivity exploring array substrates amenable methods. Furthermore, underscores exhibited their utility organic light-emitting diodes (OLEDs), stimuli-responsive materials, sensors, bioimaging, photodynamic therapy (PDT).Graphical abstract

Язык: Английский

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Catalyst-controlled directing group translocation in the site selective C–H functionalization of 3-carboxamide indoles and metallocarbenes

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Complementary methods toward the selective functionalization of indole and oxindole frameworks employing an alternative strategy in heteroaryl C–H functionalizations are presented herein. This work focuses on a catalyst-controlled, site activation/functionalization 3-acyl indoles, wherein amide serves as robust versatile directing group capable undergoing concomitant 1,2-acyl translocation/C–H presence RhI/AgI co-catalysts to provide cross-coupled adducts high yields. In contrast, use IrIII/AgI catalysts subverted migration afford corresponding C2-functionalized products good excellent A notable feature catalyst systems was exceptional level selectivity observed which functionalized indoles were obtained exclusively. Mechanistic experiments indicate concerted step metallation occurring through electrophilic aromatic substitution process. Here, authors present divergent, transition metal catalyst-controlled 3-carboxamide indoles. One set conditions enables 2-position, while other translocation carboxamide at 3-position.

Язык: Английский

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Ligand‐Controlled Nickel‐Catalyzed Regiodivergent Cross‐Electrophile Alkyl‐Alkyl Couplings of Alkyl Halides

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(7)

Опубликована: Дек. 14, 2022

Functionalizing specific positions on a saturated alkyl molecule is key challenge in synthetic chemistry. Herein, ligand-controlled regiodivergent alkylations of bromides at different by Ni-catalyzed alkyl-alkyl cross-electrophile coupling with the second has been developed. The reaction undergoes site-selective isomerization one controlled manner, providing switchable access to diverse alkylated structures sites bromides. occurs three similar excellent chemo- and regioselectivity, representing remarkable ligand tuned reactivity between cross-coupling nickel migration along hydrocarbon side chain. This offers catalytic platform architectures bond-formation from identical starting materials.

Язык: Английский

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