Transition-State Stabilization by Secondary Orbital Interactions between Fluoroalkyl Ligands and Palladium During Reductive Elimination from Palladium(aryl)(fluoroalkyl) Complexes

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(19), P. 12810 - 12825

Published: Sept. 18, 2023

Palladium-catalyzed fluoroalkylations of aryl halides are valuable reactions for the synthesis fluorinated, biologically active molecules. Reductive elimination from an intermediate Pd(aryl)(fluoroalkyl) complex is step that forms C(aryl)–C(fluoroalkyl) bond, and this typically requires higher temperatures proceeds with slower rates than reductive nonfluorinated alkylarenes analogous Pd(aryl)(alkyl) complexes. The experimental correlate poorly common parameters, such as steric property or electron-withdrawing ability fluoroalkyl ligand, making prediction rational design Pd-catalyzed difficult. Therefore, a systematic study features ligands affect barrier to key step, including properties, secondary interactions, necessary future development fluoroalkylation occur under milder conditions tolerate additional types reagents. We report computational studies effect (RF) ligand on barriers Pd(aryl)(RF) complexes (RF = CF2CN, CF2C(O)Me, etc.) containing bidentate di-tert-butyl(2-methoxyphenyl)phosphine (L). computed Gibbs free-energy these suggest fluoroalkylarenes should form quickly at room temperature we studied, excluding RF CF3, CF2Me, C2F5, CF2CFMe2, CF2Et, CF2iPr, CF2tBu. Analyses transition-state structures by natural bond orbital (NBO) independent gradient model (IGMH) approaches reveal interactions between Pd center hydrogen atom π-acid bonded α-carbon stabilize lowest-energy transition states Comparisons conformers magnitude stabilizations 4.7–9.9 kcal/mol. In absence more leads less ligand. Computations para-substituted groups palladium electron-rich tend be lower those when can engage in metal center. However, do not depend electronic properties

Language: Английский

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Cobalt-catalyzed decarboxylative difluoroalkylation of nitrophenylacetic acid salts

Chemical Science, Journal Year: 2023, Volume and Issue: 14(47), P. 13902 - 13907

Published: Jan. 1, 2023

The selective installation of fluorine-containing groups adjacent to sterically hindered alkyl has been utilized for the synthesis and derivatization biologically active molecules.

Language: Английский

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Post-Transition-State Dynamic Effects in the Transmetalation of Pd(II)-F to Pd(II)-CF₃

JACS Au, Journal Year: 2023, Volume and Issue: 4(1), P. 263 - 275

Published: Dec. 29, 2023

The observation of post-transition-state dynamic effects in the context metal-based transformation is rare. To date, there has been no reported case a effect for widely employed class palladium-mediated coupling reactions. We performed an experimental and computational study trifluoromethylation Pd

Language: Английский

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Unveiling Pre-Transmetalation Intermediates in Base-Free Suzuki–Miyaura Cross-Couplings: A Computational Study

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

The pre-transmetalation intermediates are critically important in Suzuki–Miyaura cross-coupling (SMC) reactions and have become a hot spot of the current research. However, under base-free conditions not been clear. Herein, comprehensive theoretical study is performed on Pd-catalyzed desulfonative SMC reaction. fragile coordination feature acceleration role RuPhos chelate ligand revealed. hydrogen-bond complex between Pd–F aryl boronic acid identified as an intermediate, which increases energy span to 32.5 kcal/mol. controlling factor for formation complexes attributed electronegativities halogen atoms metal halide complexes. What more, other reported reaction systems involving acids reconsidered suggest that widely exist stable with influencing catalytic activities. earth-abundant Ni-catalyzed further designed predicted higher activity than original

Language: Английский

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Palladium-Catalyzed Decarbonylative Nucleophilic Halogenation of Acyl Fluorides and Chlorides: Synthesis of Aryl Halides via Reductive Elimination of the C–X (X = I, Br, and Cl) Bond and Mechanistic Implications

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(16), P. 11905 - 11917

Published: July 25, 2024

Aryl halides are widely recognized as crucial and versatile feedstocks for organic synthesis. However, in palladium-catalyzed reactions, while oxidative addition of carbon–halogen bonds is thermodynamically favorable, the reverse reaction─reductive elimination with formation bonds─poses a significant challenge. As part conducting series decarbonylative transformations acyl halides, we developed nucleophilic halogenation fluorides chlorides through Pd-mediated reductive C–X bond. These reactions enable synthesis aryl iodides, bromides, using alkali metal halides. Regarding reaction mechanism, Xantphos ligand emerges factor promoting elimination, leading to stable Pd(0) intermediate an adduct trans-(Xantphos)Pd(ArCO)X. Two proposed mechanisms involve Xantphos-promoted outer-sphere substitution direct transhalogenation between In latter or react form corresponding iodides bromides situ under mild conditions decarbonylation, yielding desired via unimolecular fragment coupling. Importantly, it evident that controlling rate halide appropriate combination substrates success this reaction. Indeed, found gradual iodide pivotal managing undesired generation I2, known catalyst poison. This observation enables us fine-tune conditions, thereby improving selectivity transformation. result, achieve enhanced yields final products establish more sustainable robust catalytic processes. advancement not only boosts applicability reliability our synthetic methodology but also underscores potential broader adoption

Language: Английский

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