Dual ligands relay-promoted transformation of unstrained ketones to polyfluoroarenes and nitriles

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(7), P. 2037 - 2045

Published: June 20, 2023

Language: Английский

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Nondirected C–H/C–F Coupling for the Synthesis of α-Fluoro Olefinated Arenes

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(21), P. 14000 - 14011

Published: Oct. 17, 2023

The fluorinated entities are considered a privileged structure class in the field of medicinal chemistry because amplified bioactivity they exhibit. In this regard, developments C–H fluorination and trifluoromethylation have been mostly targeted. α-fluoro olefins also show potential applications as bioisosteres amides prevalent drug candidates, but their synthetic accessibility by activation strategy remains an elusive domain. assistance directing group (DG) does enable fluoroalkenylation constrains scope terms expansion chemical space for development programs. nondirected is "one-shot" solution to existing issues on use DGs. With perspective, we herein report protocol Pd-catalyzed C–H/C–F coupling accessing regioselective fashion. transformation governed dual control pyridine amino acid-based ligand, which dictate complementary selectivity achieved. allows late-stage derivatization drugs natural products enables conjugation with product means fluoro-olefin bridge. incorporation these moieties can potentially modulate parent drugs. Mechanistic investigations DFT calculations suggest vital role monoprotected acid ligand step through concerted metalation deprotonation, overall turnover frequency-determining state catalytic cycle.

Language: Английский

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Advances in Pyridine C – H Functionalizations: Beyond C2 Selectivity

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 31(2)

Published: Nov. 28, 2024

The pyridine core is a crucial component in numerous FDA-approved drugs and Environmental Protection Agency (EPA) regulated agrochemicals. It also plays significant role ligands for transition metals, alkaloids, catalysts, various organic materials with diverse properties, making it one of the most important structural frameworks. However, despite its significance, direct selective functionalization still relatively underdeveloped due to electron-deficient nature strong coordinating ability nitrogen. Among variety synthetic transformation, C-H bond straightforward atom economical approach it's advantageous late-stage containing drugs. In recent years, innovative strategies regioselective pyridines azines have emerged, offering benefits such as high regioselectivity, mild conditions, enabling transformations that were challenging traditional methods. This review emphasizes latest advancements meta para-C-H through approaches, including phosphonium salts, photocatalytic methods, temporary de-aromatization, Minisci-type reactions, metal-catalyzed activation techniques. We discuss advantages limitations these current methods aim inspire further progress this field.

Language: Английский

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Multimetallic Pd- and Ni-catalyzed C(sp²)–P cross-coupling under aqueous micellar conditions

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(23), P. 9779 - 9794

Published: Jan. 1, 2023

Multimetallic Pd/Ni and dual-ligand Pd catalysis enable C(sp 2 )–P cross-coupling reactions in aqueous micelles under mild conditions using inexpensive commercial materials catalysts while avoiding environmentally unsustainable organic solvents.

Language: Английский

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Electrochemically Driven para‐Selective C(sp²)−H Alkylation Enabled by Activation of Alkyl Halides without Sacrificial Anodes

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(25)

Published: Feb. 23, 2024

Abstract With alkyl halides (I, Br, Cl) as a coupling partner, an electrochemically driven strategy for para ‐selective C(sp 2 )−H alkylation of electron‐deficient arenes (aryl esters, aldehydes, nitriles, and ketones) has been achieved to access diverse alkylated in one step. The reaction enables the activation absence sacrificial anodes, achieving formation )‐C(sp 3 ) bonds under mild electrolytic conditions. utility this protocol is reflected high site selectivity, broad substrate scope, scalable.

Language: Английский

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Ligand-Controlled Nondirected meta- or para-C–H Olefination of Silyl-Protected Phenols

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(17), P. 12806 - 12813

Published: Aug. 9, 2024

Recent advances in ligand design have enabled Pd(II)-catalyzed nondirected C–H functionalization using arenes as the limiting reagent, but achieving catalyst control over site selectivity these transformations remains a significant challenge. Instead, is typically governed by inherent steric and electronic properties of arene substrates or directing effects. Consequently, it can be difficult to selectively functionalize para-position electron-deficient meta-positions electron-rich arenes, respectively. In this report, we demonstrate that choice olefination switch between activated para- deactivated meta-C–H bonds silyl-protected phenols, thereby highly enabling site-selective either position with broad substrate scopes. Specifically, monodentate 2-pyridone ligands enable high-yielding conventional para-selectivity largely intrinsic bias substrate, whereas dual-ligand system consisting bidentate pyridine–pyridone pyridine reversed site-selectivity favor relatively meta-position. Mechanistic studies indicate renders para-C–H palladation reversible not palladation, favoring arenes.

Language: Английский

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Synthesis of β-(Hetero)aryl Ketones via Ligand-Enabled Nondirected C–H Alkylation

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(20), P. 15654 - 15664

Published: Oct. 7, 2024

β-Aryl ketones are essential structural units in natural products and bioactive molecules, commonly synthesized through coupling reactions involving prefunctionalized arenes or via directing group (DG) strategies. However, these conventional methods often inefficient, requiring multiple synthetic steps that escalate both the cost complexity of process. The need for additional steps, such as installation subsequent removal, further compromises atom economy overall efficiency. Herein, we report a palladium(II)-catalyzed dual ligand-enabled nondirected C–H alkylation with arene heteroarene limiting reagent synthesis β-(hetero)aryl less chemical waste. combined influence 2-methyl quinoxaline N-acetyl phenylalanine ligands imparts significant surge selectivity, facilitating diversification drugs alkylation. Integrated experimental computational mechanistic studies demonstrate activation regio- rate-determining step. Interestingly, while Pd–Ag heterobimetallic species is not directly involved 1,2-migratory insertion step, it proposed to play vital role during product release phase catalytic cycle.

Language: Английский

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Palladium Catalysis: Dependence of the Efficiency of C−C Bond Formation on Carboxylate Ligand and Alkali Metal Carboxylate or Carboxylic Acid Additive. Part A: the C(sp²)−C(sp²), C(sp²)−C(sp³) and C(sp³)−C(sp³) Bonds

Advanced Synthesis & Catalysis, Journal Year: 2023, Volume and Issue: 365(22), P. 3727 - 3773

Published: Oct. 3, 2023

Abstract A variety of Pd‐catalyzed reactions are carried out with palladium carboxylates in the presence carboxylic acids and/or alkali metal carboxylates. This review is Part three reviews highlighting dependence efficiency formation different C−C bonds on nature carboxylate unit. concerns inter‐ and intramolecular leading to a C( sp 2 )−C( ), 3 ) or bond. The procedures additives presented as well reaction mechanisms with, far possible, personal comments.

Language: Английский

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Ligand-Enabled C6-Selective C–H Arylation of Pyrrolo[2,3-d] Pyrimidine Derivatives with Pd Catalysts: An Approach to the Synthesis of EGFR Inhibitor AEE-788

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(11), P. 8023 - 8034

Published: May 20, 2024

Herein, we report the Pd(II)-catalyzed direct C-H arylation of pyrrolo[2,3-

Language: Английский

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Divergent total syntheses of pyrroloiminoquinone alkaloids enabled by the development of a Larock/Buchwald–Hartwig annulation/cyclization

Chemical Science, Journal Year: 2024, Volume and Issue: 15(31), P. 12284 - 12290

Published: Jan. 1, 2024

Pyrroloiminoquinone alkaloids are a large class of natural products that display wide range biological activities. Synthetic approaches to these typically rely on common late-stage C10-oxygenated pyrroloiminoquinone intermediate, but strategies often lead lengthy synthetic sequences not amenable divergent syntheses. We devised an alternative approach aimed at the early introduction C10 nitrogen, which we hypothesized would enable diversification. This strategy hinged upon Larock/Buchwald-Hartwig annulation/cyclization quickly access core alkaloids. report development this cascade process, was facilitated by dual ligand system in addition selective functionalization key provide efficient syntheses makaluvamines A, C, and D isobatzelline B, first total synthesis makaluvamine N.

Language: Английский

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