Ligand-Enabled Gold-Catalyzed C(sp 2 )−O Cross-Coupling Reactions: A Breakthrough in Gold Catalysis

IISER Bhopal researchers has made a breakthrough in gold catalysis by developing a new method for cross-coupling reactions using ligand-enabled Au(I)/Au(III) catalysis. The study, published in ACS Catalysis, shows that a variety of aryl iodides and alcohols can be successfully synthesized in good to excellent yields.

Bullet point summary:

• New method for cross-coupling reactions using ligand-enabled Au(I)/Au(III) catalysis
• Good to excellent yields of aryl iodides and alcohols successfully synthesized
• Wide functional group tolerance
• Methoxylation of various complex and medicinally relevant molecules achieved
• Site-selective C–O cross-coupling reactions enabled with complementary site-specificity compared to Pd or Cu catalysis
• Mechanistic investigations strongly support proposed reaction mechanism
• Expected to enable development of various other challenging cross-coupling reactions in gold catalysis

IISER Bhopal researchers successfully synthesized a series of substrates bearing an electronically poor iodoarene and an electronically deficient ionodoarenes under the optimized reaction conditions, leading to the formation of C–O bonds. The corresponding products were well tolerated under the present reaction conditions and afforded in good-to-excellent yields (51-88%).

The study also found that alcohols such as ethanol, n-butanol, 2-chloroethanol, 2-(trimethylsilyl)ethanol, and 2-methoxyethanol were well compatible (61-90%) under the current reaction conditions. The success of these site-selective methoxylation reactions suggests that gold-catalyzed C–O cross-coupling offers complementary site-specificity compared to those in Cu or Pd.

The researchers also conducted mechanistic investigations including NMR and mass spectrometric studies, which strongly support the proposed mechanism of the reaction. The realization of the C–O cross-coupling reaction is expected to lay a foundation for the development of various other challenging cross-coupling reactions that remain unachieved in gold catalysis.

Overall, this breakthrough in gold catalysis offers a promising new method for cross-coupling reactions with complementary site-specificity compared to Pd or Cu catalysis. The potential for developing new and challenging cross-coupling reactions could have a significant impact on various fields, including pharmaceuticals, materials science, and organic chemistry.

Outcomes:

• Ancillary ligand-enabled gold-catalyzed C(sp2)–O cross-coupling reactions of aryl iodides with aliphatic alcohols developed.
• The reaction displays a wide functional group tolerance and has been extended for the methoxylation of various complex and medicinally relevant molecules.
• Site-selective C–O cross-coupling reactions enabled with complementary site-specificity compared to Pd or Cu catalysis.
• Mechanistic investigations including NMR and mass spectrometric studies strongly support the proposed mechanism of the reaction.
• Expected to lay a foundation for the development of various other challenging cross-coupling reactions that remain unachieved in gold catalysis.

Ligand-Enabled Gold-Catalyzed C(sp 2 )−O Cross-Coupling Reactions

Das; Patil 

Full-text link: https://doi.org/10.1021/acscatal.3c00338

What this paper is about

• Letter substrates to CO cross-coupling reactions using Au.
• When 6a was subjected under Au catalysis, CO cross-coupling product 7a was observed exclusively with electronically deficient iodoarene keeping electronically neutral iodoarene intact.
• However, under Pd or Cu catalysis, di-iodoarene 6a results in the formation of a mixture of mono-and dimethoxylated products.

What you can learn

• Furthermore, by comparing the reactivities of Pd and Cu with Au, we demonstrate the complementary reactivity of the present approach in enabling site-selective C O cross-coupling reactions.
• Moreover, mechanistic investigations including NMR and mass spectrometric studies strongly support the proposed mechanism of the reaction.
• The realization of the CO cross-coupling reaction is expected to lay a foundation for the development of various other challenging cross-coupling reactions that remain unachieved in gold catalysis.

Core Q&A related to this research

1. What is the focus of the paper “Ligand-Enabled Gold-Catalyzed C(sp2)−O Cross-Coupling Reactions”?

• The focus of the paper is the development of ligand-enabled gold-catalyzed C(sp2)−O cross-coupling reactions of aryl iodides with aliphatic alcohols.

2. What type of substrates have been successfully synthesized using ligand-enabled Au(I)/Au(III) catalysis?

• A variety of aryl iodides and alcohols have been successfully synthesized in good to excellent yields.

3. What is the advantage of using Au catalysis over Pd or Cu catalysis?

• The complementary site-specificity of Au catalysis enables site-selective C–O cross-coupling reactions.

4. What products were observed when electronically deficient iodoarene was used under Au catalysis?

• Exclusively, CO cross-coupling product was observed.

5. What does the realization of CO cross-coupling reactions using Au catalysis mean for the future of cross-coupling reactions?

• It is expected to lay a foundation for the development of various other challenging cross-coupling reactions that remain unachieved in gold catalysis.

Basics Q&A related to this research

1. What are aryl iodides?

Aryl iodides are a type of organic compound that contain an iodine atom attached to an aromatic ring.

2. What is gold catalysis?

Gold catalysis is a type of chemical reaction process that involves the use of a gold-based catalyst to enable or enhance a chemical reaction.

3. What is ligand-enabled Au(I)/Au(III) catalysis?

Ligand-enabled Au(I)/Au(III) catalysis is a chemical reaction process that involves the use of a gold-based catalyst complex with a ligand to enable the cross-coupling of aryl iodides and alcohols.

4. What are Pd, Cu, and Ni catalysts?

Pd, Cu, and Ni are transition metals that can be used as catalysts in various chemical reactions, including cross-coupling reactions.

5. What are C-O cross-coupling reactions?

C-O cross-coupling reactions are a type of chemical reaction that involves the formation of a carbon-oxygen bond between two organic compounds, typically an aryl iodide and an alcohol.

6. What are substrates in this context?

Substrates refer to the starting materials or reactants used in a chemical reaction.

7. What are electronically poor idoarene and electronically deficient ionodoarenes?

Electronically poor idoarenes and electronically deficient ionodoarenes are types of aryl iodides that are used in C-O cross-coupling reactions with alcohols.

8. What are ethanol, nbutanol, 2-chloroethanol, 2-(trimethylsilyl)ethanol, and 2-methoxyethanol?

Ethanol, nbutanol, 2-chloroethanol, 2-(trimethylsilyl)ethanol, and 2-methoxyethanol are examples of alcohols that are compatible with the current reaction conditions for C-O cross-coupling reactions.

9. What is site-specificity in this context?

Site-specificity refers to the ability of a chemical reaction to selectively form a bond at a specific site on a molecule.

10. What is complementary reactivity?

Complementary reactivity refers to the ability of a new chemical reaction approach, such as the ligand-enabled Au(I)/Au(III) catalysis, to enable the formation of a product that cannot be achieved with traditional catalysts, such as Pd or Cu.

11. What are mechanistic investigations?

Mechanistic investigations are experiments and analyses designed to study and understand the underlying chemical processes and reactions that occur during a chemical reaction.

12. What is NMR?

NMR (Nuclear Magnetic Resonance) is a technique used to study the chemical and physical properties of molecules by analyzing their interactions with a magnetic field.

13. What is mass spectrometry?

Mass spectrometry is a technique used to identify and analyze the chemical composition and structure of molecules by measuring the mass-to-charge ratio of ionized particles.

14. What is the CO cross-coupling reaction?

The CO cross-coupling reaction is a type of chemical reaction that involves the formation of a carbon-oxygen bond between two organic compounds, typically an aryl iodide and an alcohol, using a gold-based catalyst.