Dual Nickel-/Palladium-Catalyzed Reductive Cross-Coupling Reactions between Two Phenol Derivatives

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Phenols are abundant and versatile starting materials in organic synthesis.
• Developing efficient cross-coupling reactions from phenol-derived substrates is highly desirable.
• Existing methods often lack broad functional group tolerance or struggle with sterically hindered substrates.

Purpose of the Study:

• To develop a novel dual nickel/palladium-catalyzed reductive cross-coupling reaction.
• To utilize easily accessible aryl tosylates and aryl triflates derived from phenols.
• To demonstrate the reaction's broad scope, functional group tolerance, and utility in late-stage functionalization.

Main Methods:

• Dual catalysis employing nickel and palladium complexes.
• Reductive cross-coupling of aryl tosylates and aryl triflates.
• Synthesis of diverse biaryl compounds and functionalized arenes.

Main Results:

• Successful cross-coupling of aryl tosylates and aryl triflates in a single step from phenols.
• Demonstrated broad substrate scope (>60 examples) and functional group tolerance.
• Achieved efficient synthesis of sterically hindered biaryls and fully substituted aryl products.
• Applied the methodology for late-stage functionalization of pharmaceutical compounds like ezetimibe and tyrosine.

Conclusions:

• The developed dual catalytic system provides a powerful and versatile method for constructing biaryl compounds.
• This approach offers a practical route to complex molecules from readily available phenolic precursors.
• The reaction's tolerance to steric hindrance and its applicability in late-stage functionalization highlight its significance in synthetic chemistry.