Development of a Deactivation-Resistant Dialkylbiarylphosphine Ligand for Pd-Catalyzed Arylation of Secondary Amines

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 17, 2024

Despite the prevalence of N-heteroarenes in small-molecule pharmaceuticals, Pd-catalyzed C-N cross-coupling reactions aryl halides and amines containing these rings remain challenging due to their ability displace supporting ligand via coordination metal center. To address this limitation, we report development a highly robust Pd catalyst supported by new dialkylbiarylphosphine ligand, FPhos. The FPhos-supported effectively resists N-heteroarene-mediated deactivation readily promote coupling between wide variety Lewis-basic secondary amines, including densely functionalized pharmaceuticals. Mechanistic structural investigations, as well principal component analysis density functional theory, elucidated two key design features that enable FPhos overcome limitations previous ligands. First, ligated complex is stabilized through its conformational preference for O-bound isomer, which likely N-heteroarenes. Second, 3',5'-disubstitution on non-phosphorus-containing ring creates ideal steric environment around center, facilitates binding larger while mitigating formation off-cycle palladacycle species.

Язык: Английский

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Palladium(II)‐Catalyzed Nondirected Late‐Stage C(sp²)−H Deuteration of Heteroarenes Enabled Through a Multi‐Substrate Screening Approach

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(27)

Опубликована: Март 21, 2024

The importance of deuterium labelling in a variety applications, ranging from mechanistic studies to drug-discovery, has spurred immense interest the development new methods for its efficient incorporation organic, and especially bioactive molecules. five-membered heteroarenes at center this work are ubiquitous motifs molecules these compounds therefore highly desirable. However, profound differences chemical properties encountered between different hamper single set broadly applicable reaction conditions, often necessitating separate optimization campaign given type heteroarene. In study we describe use multi-substrate screening approach identify optimal conditions classes minimal number reactions. Using approach, four sets complementary derived our dual ligand-based palladium catalysts nondirected C(sp

Язык: Английский

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Plasmonic Pd-Sb nanosheets for photothermal CH ₄ conversion to HCHO and therapy

Science Advances, Год журнала: 2024, Номер 10(36)

Опубликована: Сен. 4, 2024

Photothermal catalysis effectively increases catalytic activity by using the photothermal effect of metal nanomaterials; however, combination strong light absorption and high performance remains a challenge. Here, we demonstrate hexagonal ~5-nanometer-thick palladium antimony (chemical formula as Pd 8 Sb 3 ) nanosheets (NSs) that exhibit within full spectral localized surface plasmon resonance (LSPR) effects in visible region. Such LSPR features lead to effects, NSs aqueous dispersion enables enhanced methane (CH 4 conversion formaldehyde (HCHO) under full-spectrum irradiation at 1.7 watts per square centimeter, leading selectivity ~98.7%, productivity ~665 millimoles gram catalyst, ~700 times higher than NSs. Mechanism investigations suggest different radicals were generated on (·OH) (·O 2 − ), where displays stronger adsorption strength CH facilitates oxidation HCHO. Besides, ability therapy for breast cancer.

Язык: Английский

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Construction of Bis-Heterocyclic Energetic Compounds via C–N Coupling Reactions

JACS Au, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

The C–N bonded aromatic compounds have demonstrated potential applications in energetic materials, polymers, agrochemicals, and medicinal chemistry. Developing improved methodologies for the streamlined economical generation of bonds is highly sought-after. In this study, an efficient strategy was developed to construct bis-heterocyclic compounds. A total 26 substrates with different functional groups substituted azoles were selected react 1,3,4-trinitropyrazole. results demonstrate that coupling reaction predominantly influenced by pKa substrates. relationships between products meticulously investigated determined. Among those products, 3a–3d exhibit high thermostability comparable detonation properties RDX, indicating significant use as secondary explosives. method presented work may also serve a powerful toolkit design synthesize domains chemistry organic materials.

Язык: Английский

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Palladium-Catalyzed ortho C–H Allylation of Tertiary Anilines

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Allyl groups could be transformed into various functional groups. A novel and highly regioselective approach for the Pd-catalyzed ortho C–H allylation of tertiary anilines has been developed. Various substitution were well-tolerated, allylated linezolid, ibuprofen, naproxen, ketoprofen, dehydroabietic acid derivatives easily prepared. Notably, this new method overcomes limitations classical amide-directing groups, as amide are well-tolerated in reaction. Preliminary mechanistic studies revealed that a dual-ligand effect may involved achieving excellent selectivity reaction facilitated by N-Bz-Gly Ag2CO3. Further indicate FeCl3 is necessary Lewis to activate allyl bromide.

Язык: Английский

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Spirobipyridine Ligands as a Unique Platform for Substrate Recognition and Reaction Control through Noncovalent Interactions

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 6372 - 6379

Опубликована: Апрель 4, 2025

Язык: Английский

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Comparison of Phosphonium and Sulfoxonium Ylides in Ru(II)-Catalyzed Dehydrogenative Annulations: A Density Functional Theory Study

Molecules, Год журнала: 2025, Номер 30(9), С. 1883 - 1883

Опубликована: Апрель 23, 2025

Density functional theory calculations have been performed to explore the detailed mechanism of a ruthenium-catalyzed dehydrogenative annulation between α-carbonyl phosphonium ylide (A) and sulfoxonium (B). The proposed catalytic cycles consist several elementary steps in succession, namely C–H activation A, insertion B, reductive elimination, protodemetallation, an intramolecular Wittig reaction, which is rate-limiting, with free energy barrier 31.7 kcal/mol. As A B are both capable being substrate carbene precursor, there potentially four competing pathways including homo-coupling reactions. Further demonstrate that more reactive step than while opposite conclusion true for step, can successfully explain fact solely observed product originated from use as precursor. Molecular electrostatic potential, charge decomposition, electron density difference analyses were understand distinct behaviors two ylides nature key ruthenium–carbene intermediate.

Язык: Английский

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Late-Stage C–H Deuteration of Organic Compounds via Ligand-Enabled Palladium-Catalyzed Hydrogen Isotope Exchange

Synlett, Год журнала: 2024, Номер 35(19), С. 2191 - 2200

Опубликована: Март 22, 2024

Abstract Over the past years our lab has established a research program towards late-stage introduction of deuterium into organic molecules using Pd-catalyzed reversible C–H activation as means to affect hydrogen isotope exchange. Through catalyst design, including novel ligand scaffolds, well use strategically chosen optimization and screening approaches, e.g., exploiting microscopic reversibility by first optimizing de-deuteration processes or multi-substrate approach, studies have resulted in number synthetically useful labelling protocols are described herein from personal perspective. 1 Introduction 2 β-C(sp3)–H Deuteration Free Carboxylic Acids 3 Nondirected Arenes 4 Heteroarenes 5 Conclusion

Язык: Английский

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Ligand-Enabled ortho-Selective C–H Olefination of Tertiary Aniline Derivatives

Organic Letters, Год журнала: 2024, Номер 26(23), С. 4877 - 4881

Опубликована: Июнь 5, 2024

A highly ortho-selective CAr–H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, BQ were the key factors for tuning regioselectivity from para ortho. Density functional theory used achieve theoretical understanding ortho selectivity.

Язык: Английский

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

ACS Catalysis, Год журнала: 2024, Номер 14(20), С. 15654 - 15664

Опубликована: Окт. 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.

Язык: Английский

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