Ligand Substitution, Catalyst Activation, and Oxidative Addition Studies of a Stable Dialkyl Palladium Precatalyst

Organometallics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Palladium-catalyzed cross-coupling reactions are indispensable in chemical synthesis, but efficient situ catalyst activation remains a persistent challenge. Current Pd(II) precatalysts often lead to inefficient activation, necessitating higher loadings and limiting selectivity. We investigated the ligand substitution mechanism of stable dialkyl complex (DMPDAB)Pd(CH2SiMe3)2 real-time using mass spectrometric monitoring. The introduction charge-tagged phosphine ligands enabled detection key catalytic intermediates identification off-cycle species. Our findings demonstrate low energy for dissociation DMPDAB reductive elimination (Me3SiCH2)2 resulting rapid formation monoligated LPd(0) species, active species oxidative addition. These mechanistic insights offer path toward developing more selective Pd-catalyzed processes, offering valuable guidance future design with improved performance.

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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Mechanisms and Site Selectivity of (Het)Ar–X Oxidative Addition to Pd(0) Are Controlled by Frontier Molecular Orbital Symmetry

Опубликована: Апрель 1, 2024

We report how the reaction mechanism and site-selectivity of 2-halopyridine oxidative addition to L2Pd(0) are both controlled by frontier molecular orbital symmetry. Comparing rates for pairs 2-chloro-3-EDG-pyridines / 2-chloro-5-EDG-pyridines (EDG = electron-donating group: NH2, OMe F) Pd(PCy3)2 reveals 3-EDG isomers undergo ~100 times faster than their 5-EDG counterparts (∆ΔG‡OA 10.4-11.6 kJ mol-1). Experimental computational mechanistic studies reveal that LUMO symmetries substrates control mechanism. For derivatives, high coefficients at reactive C2 position, antibonding symmetry through C2=N bond pyridine lead a nucleophilic displacement oxida-tive Conversely, derivatives has node C5–C2 plane, lead-ing minimal contribution carbon. The higher energy LUMO+1 substantial density C2, but nitrogen. This leads undergoing 3-centered insertion These effects also multihalogenated pyridines, which we investigate electron-withdrawing substituents. Incorporating simple fron-tier based descriptors quantitative multivariate linear model im-proved prediction accuracy relative substituted L2Pd(0).

Язык: Английский

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Mechanisms and Site Selectivity of (Het)Ar–X Oxidative Addition to Pd(0) Are Controlled by Frontier Molecular Orbital Symmetry

Organometallics, Год журнала: 2024, Номер unknown

Опубликована: Июль 16, 2024

Язык: Английский

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ortho‐Selective Suzuki Coupling of Dichlorophenol and Dichlorobenzylalcohol in Water under Palladium Catalysis Directed by Noncovalent Interactions and Computational Analysis

Asian Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Abstract The use of attractive noncovalent interactions is emerging as a versatile approach to address site‐selectivity challenges. Herein, we report ortho‐selective Suzuki coupling reactions in water 2,3‐dichloroarenes and 2,4‐dichloroarenes bearing hydroxy group the presence palladacycle catalyst directed by interactions. Various ortho‐substituted arylphenols arylbenzyl alcohols were obtained good excellent yields with high selectivity. Density functional theory (DFT) calculations ab initio molecular dynamics (AIMD) simulations suggested that ortho ‐selective dichlorophenols dichlorobenzyl occurred through electrostatic hydrogen bonding interactions, respectively.

Язык: Английский

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Quantitative Reactivity Models for Oxidative Addition to L2Pd(0): Additional Substrate Classes, Solvents, and Mechanistic Insights

Chemistry - A European Journal, Год журнала: 2024, Номер 30(62)

Опубликована: Авг. 20, 2024

Abstract Quantitative molecular structure‐reactivity models are useful for generating predictions to guide synthesis design, and in formulating testing mechanistic hypotheses. We report an expanded multivariate linear regression (MLR) model the rate of (hetero)aryl ( pseudo )halide oxidative addition L 2 Pd(0), here exemplified by Pd(PCy 3 ) . This builds on a prior from our group, with additional substrate classes (aryl chlorides iodides) reaction solvents (THF, toluene, THF/DMF mixture). Overall solvent effects across entire set minimal under these conditions, enabling unified MLR without introduction new descriptors beyond original five. Examining origin two electrostatic potential ESP led generation simpler, four descriptor that is suitable aryl halides, but not 2‐halopyridines. Using this we identified outlier, 2‐pyridyl triflate, which undergoes nucleophilic displacement does involve adjacent nitrogen atom. Finally, discuss relationship between C−X bond strength rates, compare intrinsic index IBSI dissociation enthalpy BDE as descriptor.

Язык: Английский

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“Large-but-flexible” palladium-NHCs complexes catalyzed site-selective Suzuki coupling of 2,5-dichloropyridine

Molecular Catalysis, Год журнала: 2024, Номер 572, С. 114758 - 114758

Опубликована: Дек. 9, 2024

Язык: Английский

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Interrogating Explicit Solvent Effects on the Mechanism and Site‐Selectivity of Aryl Halide Oxidative Addition to L2Pd(0)

Chemistry - A European Journal, Год журнала: 2024, Номер 30(62)

Опубликована: Авг. 20, 2024

Abstract We report a study of solvent effects on the rate, selectivity, and mechanism (hetero)aryl ( pseudo )halide oxidative addition to Pd(PCy 3 ) 2 as an exemplar L Pd(0) species. First, 2‐chloro‐3‐aminopyridine is observed undergo faster in toluene compared more polar solvents, which not consistent with trend we observe many other 2‐halopyridines. attribute this basicity hydrogen bonding between substrate. Greater bond donation from substrate leads electron‐rich aromatic system, therefore slower addition. demonstrate how affects rate site‐selectivity for donating substrates. Second, electron‐deficient multihalogenated pyridines exhibit improved different C−X sites undergoing by two mechanisms. The site that favours nucleophilic displacement transition state preferred over less‐polar 3‐centered state. Finally, triflates consistently highly states. This C−OTf addition, even presence reactive 2‐pyridyl halides.

Язык: Английский

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Theoretical study of Ni(0)-catalyzed intermolecular hydroamination of branched 1,3-dienes: reaction mechanism, regioselectivity, enantioselectivity, and prediction of the ligand

Journal of Molecular Modeling, Год журнала: 2024, Номер 31(1)

Опубликована: Дек. 11, 2024

Язык: Английский

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