Aromatic borylation/amidation/oxidation: a rapid route to 5-substituted 3-amidophenols

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• 5-substituted 3-amidophenols are valuable synthetic intermediates.
• Existing synthetic routes often require multiple steps and isolation of intermediates.

Purpose of the Study:

• To develop a streamlined and efficient method for synthesizing 5-substituted 3-amidophenols.
• To explore the use of C-H activation in a multi-step sequence.
• To demonstrate the broad applicability of the method with various amide partners.

Main Methods:

• Iridium-catalyzed aromatic C-H borylation of 3-substituted halobenzenes.
• Palladium-catalyzed amidation of the resulting boronic ester intermediate.
• Oxidation of the boronic ester to yield the final product.
• One-pot reaction sequence without intermediate isolation.

Main Results:

• Successful synthesis of 5-substituted 3-amidophenols.
• Demonstration of a telescoped C-H activation borylation/amidation/oxidation sequence.
• Compatibility with diverse amide coupling partners, including lactams, carbamates, and ureas.

Conclusions:

• The developed method provides an efficient and versatile route to 5-substituted 3-amidophenols.
• The one-pot strategy minimizes synthetic steps and purification efforts.
• This approach expands the synthetic utility of C-H activation in complex molecule synthesis.