![Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F51444.jpg&w=3840&q=50)
Different Oxidative Addition Mechanisms for 12- and 14-Electron Palladium(0) Explain Ligand-Controlled Divergent Site
Jacob P Norman1, Nathaniel G Larson1, Sharon R Neufeldt1
1Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717, United States.
ACS Catalysis
|August 21, 2023
Summary
Specific ligands can invert selectivity in cross-coupling reactions of dihalopyridines. This occurs by promoting unusual palladium(0) intermediates, enabling reactions at sites typically less reactive.
Area of Science:
- Organic Chemistry
- Catalysis
- Heterocyclic Chemistry
Background:
- Dihaloheteroarenes typically undergo cross-coupling at C-halide bonds adjacent to heteroatoms.
- Previous rationalizations exist for this common selectivity.
- Anomalous inverted selectivity has been reported but lacked mechanistic explanation.
Purpose of the Study:
- To provide a mechanistic explanation for inverted selectivity in dihalopyridine and dihalopyridazine cross-coupling.
- To investigate the role of specific ligands in altering reaction site preference.
- To elucidate the involvement of unusual palladium intermediates.
Main Methods:
- Experimental investigation of cross-coupling reactions with specific ligands.
- Computational studies (Density Functional Theory) to model reaction mechanisms.
- Analysis of palladium(0) intermediates and their electronic properties (HOMO symmetry).
Main Results:
- Specific ligands promote oxidative addition at a 12-electron palladium(0) intermediate.
- Computational analysis reveals differences in oxidative addition mechanisms for 12-electron and 14-electron palladium(0) species.
- The 12-electron palladium(0) pathway favors oxidative addition at sites distal to the nitrogen heteroatom, explaining the inverted selectivity.
Conclusions:
- The study provides the first mechanistic insight into inverted selectivity in dihalopyridine cross-coupling.
- Ligand control over palladium(0) electronic state (12e- vs 14e-) dictates reaction site preference.
- This work expands the understanding of regioselectivity in heterocyclic cross-coupling reactions.
More Related Videos
Related Concept Videos
02:04Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
5.9K
Diols are compounds with two hydroxyl groups. In addition to syn dihydroxylation, diols can also be synthesized through the process of anti dihydroxylation. The process involves treating an alkene with a peroxycarboxylic acid to form an epoxide. Epoxides are highly strained three-membered rings with oxygen and two carbons occupying the corners of an equilateral triangle. This step is followed by ring-opening of the epoxide in the presence of an aqueous acid to give a trans diol.
5.9K
02:35Regioselectivity of Electrophilic Additions-Peroxide Effect
8.7K
In the presence of organic peroxides, the addition of hydrogen bromide to an alkene yields the isomer that is not predicted by Markovnikov’s rule. For example, the addition of hydrogen bromide to 2-methylpropene in the presence of peroxides gives 1-bromo-2-methylpropane. This addition reaction proceeds via a free radical mechanism, which reverses the regioselectivity. The free radical reaction mechanism involves three stages: initiation, propagation, and termination.
8.7K
01:16Cycloaddition Reactions: Overview
2.6K
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
2.6K
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
10.3K
Alkenes are converted to 1,2-diols or glycols through a process called dihydroxylation. It involves the addition of two hydroxyl groups across the double bond with two different stereochemical approaches, namely anti and syn. Dihydroxylation using osmium tetroxide progresses with syn stereochemistry.
10.3K
![[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2Ffiles%2Fmedia%2Fscience-education%2Fscience-education-thumbs%2F12417.jpg&w=3840&q=75)
01:16[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
10.3K
The Diels–Alder reaction is an example of a thermal pericyclic reaction between a conjugated diene and an alkene or alkyne, commonly referred to as a dienophile. The reaction involves a concerted movement of six π electrons, four from the diene and two from the dienophile, forming an unsaturated six-membered ring. As a result, these reactions are classified as [4+2] cycloadditions.
10.3K
01:16Cycloaddition Reactions: MO Requirements for Thermal Activation
3.6K
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
3.6K