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

Published: May 28, 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).

Language: 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, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Language: Английский

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

Published: April 1, 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 substrate ligand. Here, we computationally evaluated over 150 transition structures in order determine mechanistic trends based on substrate, ligand(s), coordination number. Natural abundance 13C kinetic isotope effects provide experimental results consistent with computational predictions. Key findings include that (1) differences HOMO symmetries dictate that, although 12e– PdL strongly biased toward mechanism, 14e– PdL2 often prefers mechanism; (2) ligand electronics sterics, including bite angle, influence the preferred reaction PdL2; (3) phenyl triflate always reacts through regardless catalyst structure due stability anion inability oxygen effectively donate electron density Pd; (4) high reactivity C—X bonds adjacent nitrogen pyridine substrates relates stereoelectronic stabilization state. This work implications controlling rate selectivity catalytic couplings, demonstrate application insight chemodivergent cross-couplings bromochloroheteroarenes.

Language: Английский

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

Published: June 13, 2024

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 L2Pd(0), here exemplified by Pd(PCy3)2. 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.

Language: Английский

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

Published: June 13, 2024

We report a study of solvent effects on the rate, selectivity, and mechanism (hetero)aryl (pseudo)halide oxidative addition to Pd(PCy3)2 as an exemplar L2Pd(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 hydrogen-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.

Language: Английский

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