![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)
Regioselective C(sp2)-C(sp3) Coupling Mediated by Classical and Rollover Cyclometalation
Lorenzo Manca1, Giacomo Senzacqua1,2, Sergio Stoccoro1,2
1Dipartimento di Scienze Chimiche, Fisiche, Matematiche e Naturali, Università degli Studi di Sassari, Via Vienna 2, 07100 Sassari, Italy.
Molecules (Basel, Switzerland)
|February 10, 2024
Summary
Researchers developed a novel platinum-catalyzed coupling reaction to synthesize methyl-substituted pyridines and bipyridines. This method enables the creation of complex heterocyclic compounds through C(sp2)-C(sp3) bond formation.
Area of Science:
- Organometallic Chemistry
- Synthetic Organic Chemistry
- Catalysis
Background:
- Platinum(II) cyclometalated complexes are known catalysts but rarely facilitate C(sp2)-C(sp3) bond coupling.
- Existing methods for methyl-substituted heterocycles often lack efficiency or broad applicability.
Purpose of the Study:
- To develop a novel synthetic route for methyl-substituted pyridines and bipyridines using platinum(II) cyclometalated derivatives.
- To demonstrate the utility of oxidative addition/reductive elimination sequences for C(sp2)-C(sp3) bond formation.
- To establish the versatility of this method for various cyclometalated ligands.
Main Methods:
- A step-by-step synthesis involving rollover cyclometalation, ligand substitution, oxidative addition with methyl iodide, and reductive elimination.
- Characterization of intermediates and the final product, 3-methyl-6-phenyl-2,2'-bipyridine.
- Extension of the protocol to 2-phenylpyridine to yield 2-o-tolyl-pyridine.
Main Results:
- Successful synthesis of unprecedented 3-methyl-6-phenyl-2,2'-bipyridine via a Pt(II)/Pt(IV) catalytic cycle.
- Demonstration of a rare C(sp2)-C(sp3) bond coupling promoted by Pt(II) cyclometalated derivatives.
- Adaptation of the method for classical cyclometalated ligands, showing broad applicability.
Conclusions:
- A novel and efficient method for synthesizing methyl-substituted pyridines and bipyridines has been established.
- The developed protocol offers a versatile approach for methylating or alkylating heterocyclic compounds.
- This work expands the synthetic utility of platinum-catalyzed reactions in organometallic chemistry.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Related Concept Videos
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
8.4K
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
8.4K
01:27¹H NMR: Long-Range Coupling
1.7K
The coupling interactions of nuclei across four or more bonds are usually weak, with J values less than 1 Hz. While these are usually not observed in spectra, the presence of multiple bonds along the coupling pathway can result in observable long-range coupling.
In alkenes, spin information is communicated via σ–π overlap, as seen in allylic (four-bond) and homoallylic (five-bond) couplings. These coupling interactions are stronger when the σ bond is parallel to the alkene...
In alkenes, spin information is communicated via σ–π overlap, as seen in allylic (four-bond) and homoallylic (five-bond) couplings. These coupling interactions are stronger when the σ bond is parallel to the alkene...
1.7K
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
14.2K
If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
14.2K
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
01:22Spin–Spin Coupling: Three-Bond Coupling (Vicinal Coupling)
1.1K
Vicinal or three-bond coupling is commonly observed between protons attached to adjacent carbons. Here, nuclear spin information is primarily transferred via electron spin interactions between adjacent C‑H bond orbitals. This generally favors the antiparallel arrangement of spins, so 3J values are usually positive.
The extent of coupling depends on the C‑C bond length, the two H‑C‑C angles, any electron-withdrawing substituents, and the dihedral angle between the...
The extent of coupling depends on the C‑C bond length, the two H‑C‑C angles, any electron-withdrawing substituents, and the dihedral angle between the...
1.1K
01:17Thermal Electrocyclic Reactions: Stereochemistry
2.0K
The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
2.0K