A selenium-catalysed para-amination of phenols

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Glutathione peroxidase (GPx) is an antioxidant enzyme that utilizes selenium and sulfur for redox chemistry.
• Existing methods for phenol functionalization often involve stoichiometric sulfur reagents.

Purpose of the Study:

• To develop a novel selenium-catalyzed para-amination reaction for phenols.
• To explore the scope and limitations of this new synthetic methodology.
• To investigate the mechanism underlying the selenium-catalyzed process.

Main Methods:

• Para-amination of N-aryloxyacetamides using phenylselenyl bromide as a catalyst.
• Synthesis of N-acetyl p-aminophenols and substituted cyclodienones.
• Experimental and computational studies to elucidate the reaction mechanism.
• Demonstration of the reaction's mildness by synthesizing an AIEgen molecule.

Main Results:

• A catalytic amount of phenylselenyl bromide efficiently converts N-aryloxyacetamides to N-acetyl p-aminophenols.
• Substituted phenols yield dearomatized 4,4-disubstituted cyclodienone products.
• A weaker Se-N bond was identified as crucial for the catalytic cycle completion.
• The reaction proceeds under mild conditions, demonstrated by fluorogenic AIEgen synthesis.

Conclusions:

• Developed a new selenium-catalyzed para-amination of phenols, expanding selenium's role in organic synthesis.
• The method provides a facile route to functionalized aromatic compounds and complex structures.
• The reaction's mild conditions and broad applicability make it valuable for synthesizing diverse chemical entities.