Advances in the Synthesis and Applications of N-Heterocyclic Carbene Metal Complexes with a Focus on the Weak Base Route

Organometallics, Год журнала: 2023, Номер 42(19), С. 2692 - 2730

Опубликована: Сен. 21, 2023

N-heterocyclic carbene (NHC) ligands have evolved from being simple lab curiosities to tertiary phosphine mimics finally take center stage as unique supporting in organometallic chemistry, homogeneous catalysis, and more recently medicinal chemistry materials science applications. Some of these aspects are presented here a perspective researchers that been fascinated by the area for quite some time.

Язык: Английский

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Oxidative Addition of (Hetero)aryl (Pseudo)halides at Palladium(0): Origin and Significance of Divergent Mechanisms

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(28), С. 19249 - 19260

Опубликована: Июль 3, 2024

Two limiting mechanisms are possible for oxidative addition of (hetero)aryl (pseudo)halides at Pd(0): a 3-centered concerted and nucleophilic displacement mechanism. Until now, there has been little understanding about when each mechanism is relevant. Prior investigations to distinguish between these pathways were limited few specific combinations the substrate ligand. Here, we computationally evaluated over 180 transition structures in order determine mechanistic trends based on substrate, ligand(s), coordination number. Natural abundance

Язык: Английский

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Different Oxidative Addition Mechanisms for 12- and 14-Electron Palladium(0) Explain Ligand-Controlled Divergent Site Selectivity

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 8822 - 8828

Опубликована: Июль 8, 2022

In cross-coupling reactions, dihaloheteroarenes are usually most reactive at C─halide bonds adjacent to a heteroatom. This selectivity has been previously rationalized. However, no mechanistic explanation exists for anomalous reports in which specific ligands effect inverted with dihalopyridines and -pyridazines. Here we provide evidence that these uniquely promote oxidative addition 12e- Pd(0). Computations indicate 14e- Pd(0) can favor different mechanisms due differences their HOMO symmetries. These shown lead site preferences, where an atypical distal nitrogen.

Язык: Английский

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We Already Know Everything about Oxidative Addition to Pd(0): Do We?

ACS Catalysis, Год журнала: 2023, Номер 13(17), С. 11399 - 11421

Опубликована: Авг. 15, 2023

The oxidative addition (OA) of organic electrophiles to Pd(0) is a fundamental step in organopalladium chemistry and plays key role palladium-catalyzed cross-coupling reactions. This perspective summarizes selected mechanistic studies the Pd(0)-to-Pd(II) OA process involving halides pseudohalides with focus on systems relevant catalytic results are organized according nature supporting ligands, extracting general trends, describing most examples. formation active species from precatalysts surveyed, as well influence different that could be present under conditions process, providing guidelines facilitate understanding improvement

Язык: Английский

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C2-Selective Palladium-Catalyzed C–S Cross-Coupling of 2,4-Dihalopyrimidines

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

Опубликована: Янв. 19, 2025

Under most conditions, 2,4-dihalopyrimidines undergo substitution reactions at C4. Here we report that Pd(II) precatalysts supported by bulky N-heterocyclic carbene ligands uniquely effect C2-selective cross-coupling of 2,4-dichloropyrimidine with thiols. The regioselectivity this reaction stands in stark contrast to ∼1500 previously reported Pd-catalyzed cross-couplings favor C4 the absence other substituents on pyrimidine ring. Selectivity catalytic system herein is extremely sensitive structure precatalyst, largely due competing C4-selective nucleophilic aromatic substitution. C2-selectivity high 1° thiols and thiophenols, a range substituted dichloropyrimidines can be used. atypical selectivity transformation may facilitate diversity-oriented synthesis, as demonstrated for derivatives an antiviral agent. these C2─Cl cleavage not take place through typical oxidative addition pathway.

Язык: Английский

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Regioselective Suzuki–Miyarua Cross-Coupling for Substituted 2,4-Dibromopyridines Catalyzed by C₃-Symmetric Tripalladium Clusters

The Journal of Organic Chemistry, Год журнала: 2025, Номер 90(5), С. 1895 - 1904

Опубликована: Янв. 24, 2025

Multipalladium clusters possess peculiar structures and synergistic effects for reactivity selectivity. Herein, C3-symmetric tripalladium (1, 0.5 mol %) afford C2-regioselective SMCC of 2,4-dibromopyridine with phenylboronic acids or pinacol esters (C2:C4 up to 98:1), in contrast Pd(OAc)2 ligand-free conditions. In addition, similar C2-selectivity was achieved Sonogashira, Negishi, Kumada coupling reactions. This method highlights their powerful catalytic ability, exclusive C2-selectivity, broad substrate scope, efficient amplification, multiple ligand-exchange feasibility demonstrates that the conventional sites could be successfully regulated even reversed by catalysts.

Язык: Английский

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The Road Less Traveled: Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dihalogenated N-Heteroarenes

ACS Catalysis, Год журнала: 2022, Номер 12(19), С. 12014 - 12026

Опубликована: Сен. 19, 2022

The vast majority (≥90%) of literature reports agree on the regiochemical outcomes Pd-catalyzed cross-coupling reactions for most classes dihalogenated N-heteroarenes. Despite a well-established mechanistic rationale typical selectivity, several examples reveal that changes to catalyst can switch site leading unconventional product. In this Perspective, we survey these unusual cases in which divergent selectivity is controlled by ligands or speciation. some cases, origin inverted has been established, but others mechanism remains unknown. This Perspective concludes with discussion remaining challenges and opportunities field site-selective cross-coupling. These include developing better understanding oxidative addition mechanisms, role speciation establishing an explanation influence ring substituents outcome, inverting "stubborn" substrates, minimizing unwanted over-reaction di- polyhalogenated substrates.

Язык: Английский

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Recent advances in the application of ligands in palladium-catalyzed chemoselective coupling reactions at C–Br, C–OTf, and C–Cl sites

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(17), С. 4408 - 4436

Опубликована: Янв. 1, 2023

This article presents a comprehensive analysis of the progress in palladium-catalyzed coupling reactions, with an emphasis on how ligand characteristics affect chemoselectivity aryl (pseudo)halides.

Язык: Английский

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Pd(II) and Rh(I) Catalytic Precursors for Arene Alkenylation: Comparative Evaluation of Reactivity and Mechanism Based on Experimental and Computational Studies

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(28), С. 15507 - 15527

Опубликована: Июль 1, 2023

We combine experimental and computational investigations to compare understand catalytic arene alkenylation using the Pd(II) Rh(I) precursors Pd(OAc)2 [(η2-C2H4)2Rh(μ-OAc)]2 with arene, olefin, Cu(II) carboxylate at elevated temperatures (>120 °C). Under specific conditions, previous efforts have identified heterotrimetallic cyclic PdCu2(η2-C2H4)3(μ-OPiv)6 [(η2-C2H4)2Rh(μ-OPiv)2]2(μ-Cu) (OPiv = pivalate) species as likely active catalysts for these processes. Further studies of catalyst speciation suggest a complicated equilibrium between Cu(II)-containing complexes containing one Rh or Pd atom two atoms. At 120 °C, catalysis produces styrene >20-fold more rapidly than Pd. Also, is ∼98% selective formation, while ∼82% selective. Our indicate that has higher predilection toward olefin functionalization form undesired vinyl ester, arene/olefin coupling. However, temperatures, converts ester which proposed occur through low-valent Pd(0) clusters are formed in situ. Regardless functionality, regioselectivity mono-substituted arenes gives an approximate 2:1 meta/para ratio minimal ortho C-H activation. In contrast, selectivity significantly influenced by electronics, electron-rich giving 1:2:2 ortho/meta/para ratio, electron-deficient (α,α,α)-trifluorotoluene 3:1 functionalization. Kinetic intermolecular ethenylation competition experiments find reacts most benzene, rate does not correlate electronics. catalysis, react less benzene. These findings, combination results, consistent activation step involving significant η1-arenium character due Pd-mediated electrophilic aromatic substitution character. mechanism sensitive arene-substituent we propose indicates Rh-mediated

Язык: Английский

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Synthesis and Antifungal Activity of Stereoisomers of Mefloquine Analogs

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 15(6), С. 822 - 827

Опубликована: Май 1, 2024

Cryptococcal neoformans and Candida albicans are among the most prevalent causes of life-threatening fungal infections globally. The high mortality associated with these despite current antifungal therapy highlights need for new drugs. In our previous work, we demonstrated that an analogue clinically used antimalarial mefloquine, (8-chloro-2-(4-chlorophenyl)quinolin-4-yl)(piperidin-2-yl)methanol (4377), has both activity ability to penetrate central nervous system. Herein describe synthesis assay all four stereoisomers 4377. All retain potent erythro enantiomers having MIC values 1 4 μg/mL against C. albicans, respectively, threo enantiomers, 2 8 μg/mL, respectively. These results indicate stereochemistry piperidine methanol group is not critical properties 4377 gives guidance future medicinal chemistry optimization efforts.

Язык: Английский

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