Copper-Mediated Intramolecular Interrupted CuAAC Selanylation

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Heterocyclic Chemistry

Background:

• Fused heterocyclic compounds are crucial scaffolds in medicinal chemistry.
• Developing efficient and novel synthetic routes to complex heterocycles is an ongoing challenge.
• The synthesis of selenium-containing heterocycles offers unique biological properties.

Purpose of the Study:

• To develop a novel copper-catalyzed domino reaction for synthesizing fused benzo[4,5][1,3]selenazolo[3,2-c][1,2,3]triazoles.
• To establish a mild, efficient, and functional-group-tolerant method for constructing these unprecedented heterocyclic systems.
• To explore the scope of the reaction with various terminal alkynes, including protected and bioactive ones.

Main Methods:

• A copper-mediated domino reaction involving copper(I) catalysis.
• Utilizing 1,2-bis(2-azidoaryl)diselenides and terminal alkynes as starting materials.
• Employing microwave irradiation and environmentally benign solvents like dimethyl carbonate.

Main Results:

• The seminal synthesis of unprecedented fused benzo[4,5][1,3]selenazolo[3,2-c][1,2,3]triazoles was achieved.
• The reaction proceeds under mild conditions with broad functional group tolerance.
• The methodology was successfully applied to TMS-protected and bioactive alkynes, demonstrating its versatility.

Conclusions:

• A novel and efficient copper-catalyzed domino CuAAC intramolecular selanylation has been developed.
• This method provides access to a new class of fused selenium-containing heterocycles.
• The reaction's mild conditions, functional group tolerance, and use of green solvents make it a valuable tool in synthetic chemistry.